The ultimate goal is to clone mouse interferon genes, and use these both for the production of mouse interferon in a prokaryotic system and as specific probes for the study of the biological role of interferon. The cloning and use of the clones for analysis of interferon genes and their expression in mice, are the subject of this proposal. The cross-hybridization between mouse interferon (IFN) genes and human (IFN) cDNA probe (cloned in this laboratory) were detected under non-stringent conditions; the analysis of genomic DNA from several inbred strains of mice indicate that the mouse IFN gene exist as a multiple gene family. The cDNA clones of human IFNs were used to screen the mouse BALB/C library, and positive clones were identified, characterized, and sequenced. The cDNA clone will be obtained from the cDNA library of the poly(A) RNA isolated from the mouse cells induced to synthesize IFN. The restriction pattern of the genomic and cDNA clones will be compared to determine the presence or absence of introns and their sequences will be compared to that of human IFN genes. The cloned IFN genes will be used as specific probes. Mouse/hamster somatic cell hybrid will be used for the chromosomal assignment of IFN gene(s). The structure and function of the IFN complex (locus) will be examined using inbred and mutant strains of mice. The number of interferon genes determined and the frequency of the variation (polymorphism) examined. The variability in the inbred strains will be compared to the wild population. Specific probes (recognizing the individual interferon genes), will be constructed and used for the qualitative analysis of IFN structural genes and of IFN mRNA. The role of mouse genotype, tissue and inducers on the type of interferon polypeptide of induced will be examined. The role of IFN in pathogenicity of viral disease, autoimmune disease and virus induced neoplasia have been suggested by the use of the anti-interferon serum. The use of cloned IFN probes will allow to determine directly both the expression of interferon genes in the tissue of interest and whether there is a correlation between the synthesis specific interferon polypeptide and interferon induced pathogenicity. Thus the present study should provide a clue to the better understanding of the biological role of IFN system and its genetic control.